Donor Mesenchymal Stem Cell Infusion in Treating Patients With Acute or Chronic Graft-Versus-Host Disease After Undergoing a Donor Stem Cell Transplant

Cancer Clinical Trial

Official title:

Donor Mesenchymal Stem Cell Infusion for Treatment of Graft Versus Host Disease: A Phase I Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00361049
• Other study ID #: CWRU3Y03
• Secondary ID: P30CA043703CASE-
• Status: Completed
• Phase: Phase 1
• First received: August 3, 2006
• Last updated: November 4, 2010
• Start date: September 2004
• Est. completion date: November 2010

Study information

• Verified date: November 2010
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Donor mesenchymal stem cell infusion may be an effective treatment for acute or chronic graft-versus-host disease caused by a donor stem cell transplant.

PURPOSE: This phase I trial is studying the side effects and best dose of donor mesenchymal stem cells in treating patients with acute or chronic graft-versus-host disease after undergoing a donor stem cell transplant.

Description:

OBJECTIVES:

Primary

• Determine the safety of donor mesenchymal stem cell (MSC) infusion in patients with acute or extensive chronic graft-vs-host disease (GVHD) after undergoing HLA-identical sibling donor stem cell transplant.

Secondary

• Describe the rates of complete and partial resolution of GVHD when MSCs are used in addition to the standard GVHD therapy.

• Determine inflammatory cytokine levels, lymphocyte subsets, and donor-reactive lymphocyte numbers in blood of patients with acute GVHD prior to therapy and at 7 and 14 days post-MSC therapy.

• Determine if donor MSCs engraft in tissues inflamed by GVHD in patients who have undergone gender-mismatched transplantation.

OUTLINE: This is a multicenter, dose-escalation study of donor mesenchymal stem cells (MSC).

Within 72 hours after the initiation of medical therapy (e.g., corticosteroids, cyclosporine) for graft-vs-host disease, patients undergo donor MSC infusion over 10-15 minutes.

Cohorts of 3-6 patients receive escalating doses of donor MSCs until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Blood samples are obtained periodically and examined by immunoenzyme techniques for mixed lymphocyte reaction (as a surrogate marker for alloreactivity) and cytokine levels (TH1 [i.e., interleukin (IL)-2 and interferon-gamma], TH2 [i.e., IL-10 and IL-4], and inflammatory cytokines [i.e., tumor necrosis factor-alpha and IL-1]). Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.

After completion of study treatment, patients are followed periodically for 1 year.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: November 2010
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Developed acute graft-vs-host disease (GVHD) of clinical grade II-IV or extensive chronic GVHD after undergoing HLA-identical sibling donor hematopoietic stem cell transplant for any indication, malignant or nonmalignant

• Requires systemic immunosuppressive therapy with systemic corticosteroids (methylprednisone dose 2 mg/kg/day or equivalent) and concurrent cyclosporine or tacrolimus

• May have been enrolled on an institutional allogeneic stem cell transplant protocol using either ablative or nonmyeloablative preparative regimens

• No evidence of relapsed or progressive malignant disease at the time of GVHD

PATIENT CHARACTERISTICS:

• Not pregnant

• Negative pregnancy test

• Creatinine clearance = 20 mL/min

• Oxygen saturation = 90% on room air

• No severe or symptomatic restrictive or obstructive lung disease or respiratory failure requiring ventilator support

• No uncontrolled hypertension or congestive heart failure, active angina pectoris requiring the use of nitrates, myocardial infarction within the past 6 months, or major ventricular arrhythmia or cardiac failure requiring active treatment

• No significant organ dysfunction

• No active severe infections, including sepsis, pneumonia with hypoxemia, persistent bacteremia, or meningitis

• Fever without a source is allowed

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer
• Graft vs Host Disease

Intervention

Biological:
• graft versus host disease prophylaxis/therapy
Within 72 hours after the initiation of medical therapy (e.g., corticosteroids, cyclosporine) for graft-vs-host disease, patients undergo donor MSC infusion over 10-15 minutes.

Genetic:
• fluorescence in situ hybridization
Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.

Other:
• immunoenzyme technique
Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.
• immunohistochemistry staining method
Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.
• laboratory biomarker analysis
Tissue specimens are examined by CD45 immunohistochemistry and fluorescent in situ hybridization to detect hematopoietic and nonhematopoietic cells.

Procedure:
• in vitro-treated bone marrow transplantation
Within 72 hours after the initiation of medical therapy (e.g., corticosteroids, cyclosporine) for graft-vs-host disease, patients undergo donor MSC infusion over 10-15 minutes.
• management of therapy complications
Patients will be evaluated for clinical signs and symptoms of GVHD weekly for up to 28 days.

Locations

Country	Name	City	State
United States	Geauga Regional Hospital	Cleveland	Ohio
United States	Ireland Cancer Center at University Hosptials Case Medical Center, Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Lake/University Ireland Cancer Center	Cleveland	Ohio
United States	Mercy Cancer Center at Mercy Medical Center	Cleveland	Ohio
United States	Southwest General Health Center	Cleveland	Ohio
United States	UHHS Chagrin Highlands Medical Center	Cleveland	Ohio
United States	UHHS Westlake Medical Center	Cleveland	Ohio
United States	University Suburban Health Center	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Case Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety		Monitored for 6 hours for infusion related toxicity. Temperature, blood pressure, pulse and O2 saturation will be measured at baseline and every 10 minutes x 2, every 30 minutes x 2, and every hour x 3.	Yes
Secondary	Complete and partial resolution of graft-vs-host disease (GVHD)		Patients will be evaluated for clinical signs and symptoms of GVHD weekly for up to 28 days.	No
Secondary	Cytokine levels, lymphocyte subsets, and donor-reactive lymphocyte numbers in patients with acute GVHD		Pre-transplant, at diagnosis, 7 and 14 days after MSC infusion	No